The present invention relates to transdermal agent sampling. More particularly, this invention relates to the transdermal sampling of agents, such as glucose, body electrolytes and substances of abuse, such as but not limited to alcohol and illicit drugs. The present invention uses skin-piercing microblades to enhance the transdermal flux of the agents during transdermal sampling.
Obtaining a droplet of blood for the purpose of sampling a constituent (e.g., glucose) is commonly achieved by piercing the skin using a lancet or other blade-like element. Many such skin piercing devices are spring-driven so that the piercing is accomplished automatically by a pen or similar spring-loaded device. See for example, Suzuki et al. U.S. Pat. No. 5,368,047.
Many blood sampling devices also apply suction to the wound following piercing by the lancet. The suction assists in obtaining a blood sample of appropriate size for testing blood components such as glucose. See for example, Suzuki et al. U.S. Pat. No. 5,368,047; Swierczek U.S. Pat. No. 5,054,499; Ishibashi U.S. Pat. No. 5,320,607; Haber et al., U.S. Pat. No. 5,231,993; and Swierczek U.S. Pat. No. 5,201,324.
A partial vacuum applied to the skin has also been used in order to create suction blisters wherein the upper epidermis layer of the skin is separated from the dermis layer of the skin. To separate the epidermis from the dermis, a partial vacuum of about 0.25 atm (200 mm Hg) is applied for a period of about 2 hours. Upon separation of the epidermis from the dermis, The epidermis layer is then pierced or removed thereby exposing the underlying dermis layer for subsequent enhanced transdermal delivery of therapeutic agents such as drugs. See for example, Svedman, U.S. Pat. No. 5,441,490.
A partial vacuum has also been used in order to determine blood gas content by applying the partial vacuum to intact skin. The partial vacuum causes xe2x80x9csuction effusion fluidxe2x80x9d to appear on the skin surface and vaporization of blood gases therefrom. See for example, Kaneyoshi, U.S. Pat. No. 5,417,206.
There have been many attempts to enhance transdermal flux by mechanically puncturing the skin prior to transdermal drug delivery. See for example U.S. Pat. Nos. 5,279,544 issued to Gross et al., U.S. Pat. No. 5,250,023 issued to Lee et al., and U.S. Pat. No. 3,964,482 issued to Gerstel et al. These devices utilize tubular or cylindrical structures generally, although Gerstel does disclose the use of other shapes, to pierce the outer layer of the skin. Each of these devices provide manufacturing challenges, limited mechanical attachment of the structure to the skin, and/or undesirable irritation of the skin.
In addition to sampling blood, attempts have been made to sample interstitial fluid and to correlate the analyte content in the interstitial fluid with that in the blood. See for example, Joseph, U.S. Pat. No. 5,161,532; Erickson et al., U.S. Pat. No. 5,582,184; Brinda, U.S. Pat. No. 5,682,233; Erickson et al., U.S. Pat. No. 5,746,217 and Erickson et al., U.S. Pat. No. 5,820,570. One of the advantages of sampling interstitial fluid is that the wound created in the skin is not as deep as the wound needed for a blood sampling. Thus, interstitial fluid sampling is generally considered less invasive than blood sampling.
However, there is still a need for even less invasive sampling of interstitial fluid for the purpose of determining analyte concentrations in the blood, for example, blood glucose concentrations. Unfortunately, less invasive techniques tend to draw smaller and smaller fluid samples making accurate analyte concentration analysis problematic.
The present invention provides a reproducible, high volume production, low-cost device suitable for transdermal analyte sampling. The invention comprises a plurality of microblades for piercing the skin. The microblades typically have a length of less than about 0.4 mm and a width and thickness which is even smaller. In spite of their small size, the microblades can be made with an extremely reproducible size and shape so that the microslits formed by the microblades puncturing the skin also have a very reproducible size and depth. Because the microblades have a small thickness (i.e., small relative to the width and length of the microblade), the microblades produce less tissue damage for a given cross-section than a skin piercing microneedle having a circular cross-section. The device of the present invention pierces the stratum corneum of a body surface to form pathways through which a substance (e.g., a body analyte such as glucose) can be withdrawn (i.e., sampled). The device of the present invention is used in connection with body analyte or drug sampling. The sampling device used with the present invention is a negative pressure driven device which applies a partial vacuum (also referred to herein as xe2x80x9cnegative pressurexe2x80x9d) to the microslit skin. The negative pressure causes interstitial fluid to efflux from the micrcoslits. The interstitial fluid is collected and analyzed for content and/or concentration of a body analyte such as glucose.
In one aspect of the invention, the device comprises a sheet having a plurality of openings therethrough, and a plurality of microblades integral therewith and extending downward therefrom. The negative pressure driven device applies negative pressure (i.e., suction) to the microslits through the openings in the sheet.
The device is optionally anchored to the body surface in any of a plurality of ways, including but not limited to, prongs or barbs on the microblades, and skin-contact adhesives.